Neuroendocrine Carcinoma of the Bladder
Primary neuroendocrine cancer of the bladder is a rare histological occurrence, constituting 0.48–1% of all bladder cancers. The 5-year survival rate is around 8% and the prognosis is extremely unfavorable. Due to the morphology of the tumor, treatments based on small cell lung cancer have been performed. In this study, we treated a case in which chemotherapy was performed with cisplatin (CDDP) and etoposide (VP-16) forneuroendocrine cancer that occurred in the bladder; here, we report the results.
Materials and Methods
Our patient was a 49 year old male. His previous history included hypertension. He had no family history in particular. In June 2014, the patient visited our department because of voiding obstructive and irritative symptoms. He was evaluated by ultrasound examination, thoracic and pelvic CT scan, urinary cytology and cystoscopy without evidence of bladder pathology. He was treated with alpha lytic therapy because of his obstructive symptoms. Nine months later he returned with intensive irritative voiding symptoms and haematuria. An ultrasound examination revealed a thickening on the right bladder wall. A thoracic and pelvic CT scan revealed a flat lesion of 4 cm on the right bladder wall and metastasis to right external iliac lymph nodes with a diameter of 2.5 cm, resulting in a diagnosis of clinical stage T3bN1M0. No obvious distal metastasis was detected by bone scintigraphy and thoracic pelvic CT. In April 2015 the patient was hospitalized for the purpose of undergoing a transurethral resection of the bladder tumor (TUR-Bt). In the histopathological findings, there were a number of large and small solid alveoli of atypical cells accompanied by infiltrative growth into the interstitium. The atypical cells had a high N/C ratio and rough chromatin, and the neoplastic alveoli also suggested differentiation into the neuroendocrine system. When immunohistological staining was performed, the tumor cells were partially positive for CD56 and chromogranin A and negative for synaptophysin. Based on the morphology and the results of immunohistological staining, the patient was diagnosed with neuroendocrine cancer. Radical cystectomy was performed in June 2015 with bilateral ureterocutaneostomy.
In September 2015 a positron emission tomography-computed tomography (PETCT) performed before chemotherapy revealed no distal metastasis. Based on the protocol for small cell lung cancer, chemotherapy with cisplatin (CDDP) and etoposide (VP-16) was performed along with PE therapy (P: 80 mg/body, E: 100 mg/body). Two other PETCT in March 2016 and November 2016 revealed no recurrence.
Since first being reported by Cramer et al. in 1981, neuroendocrine bladder cancer has often been reported as primary small cell cancer of the bladder. Histologically, it is believed that this condition exhibits a similar histological appearance as small cell lung cancer, where the tumor cells are small, the nuclei are rich in chromatin and are circular or spindle-shaped, and tumor cells with scarce cytoplasm solidly proliferate. For immunostaining, CD56, synaptophysin, and chromogranin A are used. In this study, CD56 and chromogranin A were shown to be partially positive. The case in this study involved a high-grade neuroendocrine cancer according to the World Health Organization classification, and using the classifications of lung cancer, many parts had morphologies equivalent to those of small cell cancer, while some parts exhibited morphologies of large cell cancer. Blomjous et al. have reported that primary neuroendocrine cancer of the bladder constitutes approximately 0.48% of all bladder tumors in autopsy cases. At the time of diagnosis, primary neuroendocrine cancer of the bladder is detected as an advanced cancer occurring in T3 and T4 in 70% and 16.3% of cases, respectively. In addition, the 5-year survival rate has been reported to be 8.1–19%, and the prognosis is extremely unfavorable. Regarding treatment, multimodality therapy combining surgical therapy and chemotherapy/radiation therapy is often implemented; however, this is not yet an established therapy. Based on cases of small cell lung cancer, chemotherapy is mainly performed with PE therapy using a combination of cisplatin (CDDP) and etoposide (VP-16), and there are reports in which the prognosis was improved.
Primary neuroendocrine cancer of the bladder is a rare histological occurrence, constituting 0.48–1% of all bladder cancers. The 5-year survival rate is around 8% and the prognosis is extremely unfavorable. This case is to be signaled because of the age of the patient and the rapid evolution of pathology.
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